A neuron has a neurite extending to contact another neuron, and neuronal function is served by the propagation of neuronal activity through this contact. In the central nervous system composed of the brain and spinal cord, most of neurites are covered with the myelin sheath. The myelin sheath promotes saltatory conduction of neuronal activity to accelerate the propagation of neuronal activity, and also contributes to the maintenance of the homeostasis of axons inside the myelin sheath.
It is known that a breakdown of transmission of neuronal activity due to the removal of myelin sheath causes the appearance of diverse neurological symptoms, leading to the onset of a neurological disease referred to as a demyelinating disease. Demyelinating diseases are broadly classified into two categories: demyelinating diseases of the central nervous system such as multiple sclerosis and acute disseminated encephalomyelitis; and demyelinating diseases of the peripheral nervous system such as Guillain-Barre syndrome and chronic inflammatory demyelinating polyradiculoneuritis. Multiple sclerosis, which is one of the demyelinating diseases of the central nervous system, is characterized by temporal and spatial development of demyelination lesions due to abnormal activation of the autoimmune system. Symptoms that appear include visual disturbances, sensory disturbances, motor dysfunction, and autonomic disturbances. The prevalence of multiple sclerosis in Japan is said to be 8 to 9 in 100,000 people, and there are about 12,000 to 16,000 people affected with multiple sclerosis within the country. Hence, the establishment of a fundamental therapeutic method for a demyelinating disease such as multiple sclerosis is an urgent issue.
It is known that the myelin sheath is formed through the proliferation, migration, and differentiation of oligodendrocyte precursor cells. For the treatment of demyelinating diseases, therefore, it would be effective to repair the removed myelin sheath by promoting the proliferation of oligodendrocyte precursor cells. However, no drug has been previously developed that can promote the proliferation of oligodendrocyte precursor cells, and the treatment of demyelinating diseases mainly involves palliative treatments such as the administration of steroids and immunosuppressants, and rehabilitation. Thus, no fundamental therapeutic method has been established yet.
On the other hand, fibroblast growth factors (FGFs) are known as growth factors involved in neovascularization, wound healing, and cell proliferation. There are 23 subtypes of FGFs; one of the subtypes, FGF21, is highly expressed in the liver and pancreas, and has been shown to have diverse activities such as nutrient intake, lipolysis, glucose metabolism, and biological clock control. Furthermore, in recent years, there has been an attempt to use FGF21 as a therapeutic agent for obesity, diabetes, pancreatitis, dyslipidemia, nonalcoholic steatohepatitis (NASH), insulin resistance, hyperinsulinemia, glucose intolerance, hyperglycemia, metabolic syndrome, and the like (Patent Literature 1, for example). However, an effect of FGF21 on the proliferation of oligodendrocyte precursor cells has been hitherto unknown.